The present invention concerns a process for biotechnological preparation of arylalkanoic acids resolved in the form of optical S(+) and R(-) isomers.
More particularly, the present invention relates to the biotechnological preparation of .alpha.-arylalkanoic acids substantially in the form of an optical S(+) isomer.
Prior to the present invention, as illustrated by the work of T. Y. Shen, Angew Chem, Int. Ed. Engl., 11, 460, 1972 there are known .alpha.-arylalkanoic acids and, in particular, .alpha.-arylpropionic acids used clinically as non-steroideic anti-inflammatory agents.
The above-mentioned .alpha.-arylalkanoic acids having in position .alpha. a centre of asymmetry, appear in two optically active S(+) and R(-) enantiomeric forms.
Moreover, it is also known from the Shen publication that the anti-inflammatory activity of one of the enantiomers is greater than the other, as in the case of a number of members of the class of .alpha.-methyl-arylacetic acids known by the trade mark: Ibuprofen, Naproxen, Fenoprofen, etc.
Usually, the S(+) enantiomer develops an activity superior to the one of the R(-) enantiomer, as in the case of Ibuprofen (S. S. Adams et al., in Journal Pharm. Pharmacy 28, 256, 1976) or as in the case of Naproxen, in which the activity of the S(+) enantiomer is about 28 times greater than that of the R(-) enantiomer.
It is likewise known to separate the optical isomers of said acids, for example from an article by: D. G. Kaiser et al., in J. Pharm, Science, 2, 269, 1976; and from A. Frank and C. Ruchards in Chemistry Letter, 1431-1434, 1984.
However, the known methods for resolving the two optical isomers have drawbacks from a commercial point of view in that they are complicated, need costly optically active reactants, such as for example the kyral agents like methylbenzylamine, and do not allow, in many cases, the attainment of satisfactory yields.
Thus, there has been a long felt need for the provision of a method that would allow the resolution of the optical isomers of above mentioned acids in a simple and cheap way, and that, also would be efficient and commercially feasible.